Differences in risk profile associated with varicose veins and chronic venous insufficiency - results from the Bonn Vein Study 1.

Background: The aim of this publication is to demonstrate similarities and differences in the association of risk factors with the prevalence of different manifestations of chronic venous disease (CVD), like varicose veins (VV), venous oedema (C3) and severe chronic venous insufficiency (CVI) in the population-based cross-sectional Bonn Vein Study 1 (BVS). Patients and methods: In the BVS 1 between 13.11.2000 and 15.3.2002, 3.072 participants, 1350 men and 1722 women, from a simple random sample of the general population of the city of Bonn and two rural townships aged 18-79 years were included. The overall response proportion was 59%. All participants answered a standardized questionnaire including information about socio-economic data, lifestyle, physical activity, medical history, and quality of life. Venous investigations were performed clinically and by a standardized duplex examination by trained investigators. The CEAP classification in the version of 1996 was used to classify the findings. Logistic regression models were performed for the association of possible risk factors with VV, venous edema (C3) and severe CVI (C4-C6). The predictive risk (PR) describes the association of the diseases and the possible influencing factors. Results: VV, venous oedema (C3) and severe CVI (C4-C6) have common risk factors like higher age, number of pregnancies, family history of VV and overweight or obesity. Female gender is significantly associated with VV and C3 but not with severe CVI (C4-C6). High blood pressure and urban living are only associated with C3 and C4-C6 disease whereas prolonged sitting is associated with C3 and lower social class with C4-C6 exclusively. Discussion: In many epidemiological studies risk factors were associated with chronic venous disorders in general. Our data show that VV, venous edema and severe CVI may have different risk profiles. Venous edema is more often associated with arterial hypertension and sedentary lifestyle whereas lower social class seems to be a risk factor for severe CVI including venous ulcers. Conclusions: The differences in the association of risk factors to VV, venous edema and severe CVI should be considered if prevention and treatment of chronic venous diseases are planned. As examples, compression stockings could be proposed in sitting profession to prevent oedema, VV patients with risk factors like obesity might benefit from early treatment for VV and obesity. More longitudinal evaluation of risk factors is necessary to evaluate the true risk profile of CVD.

In Vitro Analysis of Human Cartilage Infiltrated by Hydrogels and Hydrogel-Encapsulated Chondrocytes.

Osteoarthritis (OA) is a degenerative joint disease causing loss of articular cartilage and structural damage in all joint tissues. Given the limited regenerative capacity of articular cartilage, methods to support the native structural properties of articular cartilage are highly anticipated. The aim of this study was to infiltrate zwitterionic monomer solutions into human OA-cartilage explants to replace lost proteoglycans. The study included polymerization and deposition of methacryloyloxyethyl-phosphorylcholine- and a novel sulfobetaine-methacrylate-based monomer solution within ex vivo human OA-cartilage explants and the encapsulation of isolated chondrocytes within hydrogels and the corresponding effects on chondrocyte viability. The results demonstrated that zwitterionic cartilage-hydrogel networks are formed by infiltration. In general, cytotoxic effects of the monomer solutions were observed, as was a time-dependent infiltration behavior into the tissue accompanied by increasing cell death and penetration depth. The successful deposition of zwitterionic hydrogels within OA cartilage identifies the infiltration method as a potential future therapeutic option for the repair/replacement of OA-cartilage extracellular suprastructure. Due to the toxic effects of the monomer solutions, the focus should be on sealing the OA-cartilage surface, instead of complete infiltration. An alternative treatment option for focal cartilage defects could be the usage of monomer solutions, especially the novel generated sulfobetaine-methacrylate-based monomer solution, as bionic for cell-based 3D bioprintable hydrogels.

Characterizing Intraindividual Podocyte Morphology In Vitro with Different Innovative Microscopic and Spectroscopic Techniques.

Podocytes are critical components of the glomerular filtration barrier, sitting on the outside of the glomerular basement membrane. Primary and secondary foot processes are characteristic for podocytes, but cell processes that develop in culture were not studied much in the past. Moreover, protocols for diverse visualization methods mostly can only be used for one technique, due to differences in fixation, drying and handling. However, we detected by single-cell RNA sequencing (scRNAseq) analysis that cells reveal high variability in genes involved in cell type-specific morphology, even within one cell culture dish, highlighting the need for a compatible protocol that allows measuring the same cell with different methods. Here, we developed a new serial and correlative approach by using a combination of a wide variety of microscopic and spectroscopic techniques in the same cell for a better understanding of podocyte morphology. In detail, the protocol allowed for the sequential analysis of identical cells with light microscopy (LM), Raman spectroscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). Skipping the fixation and drying process, the protocol was also compatible with scanning ion-conductance microscopy (SICM), allowing the determination of podocyte surface topography of nanometer-range in living cells. With the help of nanoGPS Oxyo®, tracking concordant regions of interest of untreated podocytes and podocytes stressed with TGF-ß were analyzed with LM, SEM, Raman spectroscopy, AFM and SICM, and revealed significant morphological alterations, including retraction of podocyte process, changes in cell surface morphology and loss of cell-cell contacts, as well as variations in lipid and protein content in TGF-ß treated cells. The combination of these consecutive techniques on the same cells provides a comprehensive understanding of podocyte morphology. Additionally, the results can also be used to train automated intelligence networks to predict various outcomes related to podocyte injury in the future.